Interaction of the pRB-family proteins with factors containing paired-like homeodomains.
The specific loss of pRB or p107 together with p130 disrupts the normal development of only a very limited spectrum of tissues. These developmental defects have been attributed primarily to deregulation of E2F activity and consequent uncontrolled proliferation. We hypothesized, however, that the tissue-specific nature of these defects may also reflect deregulation of pRB-family associated factors that are specifically involved in determining cell fate. We report here that the pRB-family members interact with transcription factors which contain paired-like homeodomains such as MHox, Chx10 and Pax-3. The interaction between the pRB-family and the paired-like homeodomain proteins was initially identified in a yeast two-hybrid screen where the N-terminal portion of p130 was used to isolate interacting factors from an embryonic mouse library. This interaction was confirmed by in vitro binding and co-immunoprecipitation assays. We show further that co-expression of Pax-3 dependent pRB, p107 or p130 with Pax-3 causes repression of activated transcription from the c-met promoter. These data demonstrate that the pRB-family proteins can modulate the activity of factors which specifically control cell fate and/or differentiation as well as controlling cell cycle regulators.
Wiggan
O
O
Department of Pathology, University of Toronto, Ontario, Canada.
Taniguchi-Sidle
A
A
Hamel
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D018398:Homeodomain Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D018398:Homeodomain Proteins; D016160:Retinoblastoma Protein